BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

Bo Ram Kim; Sang Cheul Oh; Dae Hee Lee; Jung Lim Kim; Suk Young Lee; Myoung Hee Kang; Sun Il Lee; Sanghee Kang; Sung Yup Joung; Byung Wook Min

doi:10.1007/s13277-015-3681-y

BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

Bo Ram Kim, Sang Cheul Oh, Dae Hee Lee, Jung Lim Kim, Suk Young Lee, Myoung Hee Kang, Sun Il Lee, Sanghee Kang, Sung Yup Joung, Byung Wook Min

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres’ cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

Original language	English
Pages (from-to)	9475-9486
Number of pages	12
Journal	Tumor Biology
Volume	36
Issue number	12
DOIs	https://doi.org/10.1007/s13277-015-3681-y
Publication status	Published - 2015 Dec 1

Keywords

Bone morphogenetic proteins
Cancer stem cells
Colon cancer
Epithelial-mesenchymal transition
Signal transducer and activator of transcription 3

ASJC Scopus subject areas

Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s13277-015-3681-y

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title = "BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation",

abstract = "Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres{\textquoteright} cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.",

keywords = "Bone morphogenetic proteins, Cancer stem cells, Colon cancer, Epithelial-mesenchymal transition, Signal transducer and activator of transcription 3",

author = "Kim, {Bo Ram} and Oh, {Sang Cheul} and Lee, {Dae Hee} and Kim, {Jung Lim} and Lee, {Suk Young} and Kang, {Myoung Hee} and Lee, {Sun Il} and Sanghee Kang and Joung, {Sung Yup} and Min, {Byung Wook}",

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doi = "10.1007/s13277-015-3681-y",

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T1 - BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

AU - Kim, Bo Ram

AU - Oh, Sang Cheul

AU - Lee, Dae Hee

AU - Kim, Jung Lim

AU - Lee, Suk Young

AU - Kang, Myoung Hee

AU - Lee, Sun Il

AU - Kang, Sanghee

AU - Joung, Sung Yup

AU - Min, Byung Wook

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres’ cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

AB - Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres’ cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

KW - Bone morphogenetic proteins

KW - Cancer stem cells

KW - Colon cancer

KW - Epithelial-mesenchymal transition

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BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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